Common expression of a tumor necrosis factor resistance mechanism among gynecological malignancies.
The efficacy of tumor necrosis factor alpha (TNF alpha) as an anticancer agent is limited. This limitation might be related to the expression of a protein-synthesis-dependent resistance mechanism that prevents the lysis of tumor cells by TNF alpha. To test this possibility eight randomly selected human cell lines, three derived from ovarian carcinomas and five derived from cervical carcinomas, were tested for their in vitro sensitivity to TNF alpha-mediated lysis. The results of this analysis showed that all eight cell lines are normally resistant to lysis by TNF alpha. However, in the presence of inhibitors of protein synthesis, seven of them showed a significant increase in TNF alpha-mediated lysis. Measurement of protein synthesis showed that there is a linear correlation between the level of inhibition of protein synthesis and the level of TNF alpha-mediated lysis. The fact that seven of eight randomly selected cell lines are resistant to TNF alpha because they express a protein-synthesis-dependent resistance mechanism suggests that this mechanism of resistance may be common among gynecological cancers. The results also suggest that a therapy involving TNF alpha and inhibitors of protein synthesis might be useful for the treatment of gynecological malignancies.
Powell
C B
CB
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110.
Mutch
D G
DG
Massad
L S
LS
Kao
M S
MS
Collins
J L
JL
D000912:Antibodies, Neoplasm / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000912:Antibodies, Neoplasm; D007106:Immune Sera; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide